IL-2 produced by HBV-specific T cells as a biomarker of viral control and predictor of response to PD-1 therapy across clinical phases of chronic hepatitis B

作者：Conan Chua, Loghman Salimzadeh, Ann T., Oyedele Adeyi, Hobin Seo, Giselle M. Boukhaled, Aman Mehrotra, Anjali Patel, Sara Ferrando‐Martínez, Scott H. Robbins, Danie La, David Wong, Harry L.A. Janssen, David G. Brooks, Jordan J. Feld, Adam J. Gehring · 发表于：Hepatology Communications · 年份：2023 · DOI：10.1097/hc9.0000000000000337 · 被引用次数：21 · 研究领域：Hepatitis B Virus Studies、Cancer Immunotherapy and Biomarkers、Hepatitis C virus research

BACKGROUND: There are no immunological biomarkers that predict control of chronic hepatitis B (CHB). The lack of immune biomarkers raises concerns for therapies targeting PD-1/PD-L1 because they have the potential for immune-related adverse events. Defining specific immune functions associated with control of HBV replication could identify patients likely to respond to anti-PD-1/PD-L1 therapies and achieve a durable functional cure. METHODS: We enrolled immunotolerant, HBeAg+ immune-active (IA+), HBeAg- immune-active (IA-), inactive carriers, and functionally cured patients to test ex vivo PD-1 blockade on HBV-specific T cell functionality. Peripheral blood mononuclear cells were stimulated with overlapping peptides covering HBV proteins +/-α-PD-1 blockade. Functional T cells were measured using a 2-color FluoroSpot assay for interferon-γ and IL-2. Ex vivo functional restoration was compared to the interferon response capacity assay, which predicts overall survival in cancer patients receiving checkpoint inhibitors. RESULTS: Ex vivo interferon-γ+ responses did not differ across clinical phases. IL-2+ responses were significantly higher in patients with better viral control and preferentially restored with PD-1 blockade. Inactive carrier patients displayed the greatest increase in IL-2 production, which was dominated by CD4 T cell and response to the HBcAg. The interferon response capacity assay significantly correlated with the degree of HBV-specific T cell restoration. CONCL...